To investigate the effect of homocysteine (Hcy) on cerebral perfusion and cognitive function in patients with arteriosclerotic cerebral small vessel disease (aCSVD).

A total of 117 patients with aCSVD who visited the First Affiliated Hospital of Anhui Medical University from June 2020 to September 2022 were enrolled and divided into the aCSVD cognitive impairment group (aCSVD-CI, n=57) and aCSVD non-cognitive impairment group (aCSVD-NCI, n=60) according to the Montreal Cognitive Assessment score. Serum Hcy measurement, cognitive function assessment, and three-dimensional pseudo-continuous arterial spin labeling perfusion imaging scan were performed in all patients, and multivariate Logistic regression analysis was used to explore risk factors for cognitive impairment in patients with aCSVD. The cerebral blood flow and perfusion differential brain regions of the whole brain, grey matter, and white matter were compared between the two groups. Partial correlation analyses were performed between the serum Hcy, overall cognitive function scores and cerebral blood flow in grey matter, as well as between the cerebral blood flow in the perfusion differential brain area and cognitive function scores. The mediating effect model was used to analyze the role of grey matter blood flow in the relationship between serum Hcy and overall cognition.

The serum Hcy level in the CSVD-CI group was higher than that in the CSVD-NCI group [16.38(14.02, 18.58) μmol/L vs 14.40 (11.93, 15.73) μmol/L, Z=-3.81, P<0.001]. In terms of cerebral perfusion, compared with the aCSVD-NCI group, the aCSVD-CI group had significantly lower cerebral blood flow in grey matter (Z=-3.22, P=0.001), left middle frontal gyrus (t=-4.91, P<0.05), right middle frontal gyrus (t=-5.14, P<0.05), and right orbital medial frontal lobe (t=-4.38, P<0.05). In contrast, the left hippocampus (t=4.58, P<0.05) had increased cerebral blood flow. Multivariate Logistic regression analysis showed that serum Hcy level was independent risk factor for cognitive impairment in aCSVD after controlling for multiple risk factors. Partial correlation analysis showed that left middle frontal gyrus blood flow (r=-0.39, P=0.006), right middle frontal gyrus blood flow (r=-0.44, P=0.002), and right orbital medial frontal lobe cerebral blood flow (r=-0.43, P=0.002) were negatively correlated with the Stroop Color Word Test-C results. Left hippocampal cerebral blood flow was negatively correlated with Auditory Word Learning Test-long-delayed recall (r=-0.43, P=0.002). Further mediation analysis showed that the effect of Hcy on cognitive function was partly mediated by grey matter cerebral blood flow (indirect effect=-0.11, P<0.001).

Hcy is an independent risk factor for cognitive impairment in aCSVD, and part of the effect of elevated Hcy on cognitive impairment in aCSVD may be mediated by decreased gray matter cerebral perfusion.

Cerebral small vessel diseases; Homocysteine; Cognition disorders; Arterial spin labeling; Cerebral perfusion